Abstract 2016P
Background
Recommended treatment for MIBC is radical cystectomy (RC) with cisplatin-based NAD chemotherapy in eligible patients. EFS, a common intermediate endpoint in NAD/perioperative oncology trials, allows for accelerated treatment evaluation while awaiting overall OS results. This study evaluated EFS as a clinical surrogate endpoint for OS in NAD treated MIBC.
Methods
A literature review was conducted to identify clinical trials for NAD therapy prior to RC in MIBC (stage T2-T4a, N0-N1, M0). The trial-level surrogacy was evaluated by assessing the association of hazard ratio (HR) of EFS with the HR of OS; outcome-level surrogacy was evaluated by assessing the associations of survival rates and median survival time between EFS and OS, respectively. These associations were meta-analyzed using linear regression weighted by study sample size. The strength of the association was measured by coefficient of determination (R2). Surrogate threshold effect (STE) was reported indicating the minimum HR of EFS needed to predict a significant HR of OS <1.
Results
A total of 15 eligible clinical trials were identified. The analysis of trial-level surrogacy included 6 RCTs with a total of 1,948 patients; the analyses of outcome-level surrogacy included 21 study arms from 15 trials with 2,509 patients. The log (HR) of EFS was significantly associated with the log (HR) of OS with R2 of 0.94. (Table) The STE was 0.88 for the HR of EFS. Consistently, significant outcome-level associations were observed between 3-year EFS and 5-year OS, median EFS time and median OS time, as well as 1-year EFS and 3-year OS, with R2 ranging from 0.70 to 0.97. (Table) Table: 2016P
Trial-level and outcome-level associations between EFS and OS based on clinical trials for neoadjuvant therapy in MIBC
| Outcomes for comparison | N of observations | Coefficient (P-value) | R 2 (95% CI) | |
| Trial-level surrogacy | HR of EFS vs. HR of OS | 6 RCTs | 1.26 (0.001) | 0.94 (0.74, 1.00) |
| Outcome-level surrogacy | 3-year EFS vs. 5-year OS | 12 study arms | 0.85 (ConclusionsThere is a strong association between EFS and OS in terms of treatment effects and outcome measures in clinical trials for MIBC following NAD therapy. EFS can be considered as a surrogate endpoint for OS for treatment evaluation in the NAD setting for MIBC. Clinical trial identificationEditorial acknowledgementLegal entity responsible for the studyMerck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. FundingMerck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. DisclosureC.N. Sternberg: Financial Interests, Personal, Other, Honoraria: Merck & Co., Inc., Astellas Pharma, Inc., AstraZeneca, Bayer, Bristol Myers Squibb/Medarex, Foundation Medicine Inc, Sanofi, Genzyme, Gilead Sciences, Inc., Pfizer, Janssen, Roche, Medscape, UroToday. P.J. Squires, H. Li: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. Y. Song, A. Wu, Y. Gao, C. Xu: Financial Interests, Institutional, Other, Employee of Analysis Group, Inc., which has received consultation fees from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA for conducting this work: Merck Sharp & Dohme LLC. R. Kataria: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC. Resources from the same session242P - Clinical outcomes in patients (pts) with HR+/HER2− early breast cancer (EBC) by prior systemic treatment (tx): A subgroup analysis of the NATALEE trialPresenter: Nicholas McAndrew Session: Poster session 13 243P - Prognosis of patients with hormone receptor-positive/HER2-negative early breast cancer according to monarchE and NATALEE trials risk categories: Patient-level analysis of Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) randomised trialsPresenter: Luca Arecco Session: Poster session 13 244P - Efficacy and safety of dalpiciclib, exemestane, and goserelin as neoadjuvant therapy in premenopausal HR-positive, HER2-negative breast cancer patients: A phase II clinical trialPresenter: Yang Zhengjun Session: Poster session 13 245P - Characteristics of real-world (RW) NATALEE and monarchE eligible populations: A US electronic health records (EHR) database analysisPresenter: Paolo Tarantino Session: Poster session 13 246P - Axillary management and outcomes after neoadjuvant endocrine therapy in the randomized PELOPS trialPresenter: Anna C. Weiss Session: Poster session 13 247P - Concurrent versus sequential adjuvant chemoradiotherapy in early-stage breast cancer: A systematic review and meta-analysisPresenter: Luiz Felipe de Almeida Session: Poster session 13 248P - Impact of unilateral mastectomy with or without immediate breast reconstruction on vertebral alignmentPresenter: Jong-Ho Cheun Session: Poster session 13 249P - Neoadjuvant chemotherapy in inflammatory breast cancer: A meta-analysis of 10 trials of the German Breast Group (GBG)Presenter: Laura Michel Session: Poster session 13 250P - Development and validation of a 19-feature classifier that predicts response to neoadjuvant trastuzumab emtansine (T-DM1) in breast cancer patientsPresenter: Fresia Pareja Session: Poster session 13 This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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